Measurable residual disease is not a universally reliable surrogate for progression-free survival in clinical trials of new chronic lymphocytic leukemia therapies.

At the individual-level subjects with detectable MRD (dMRD) had a significantly higher risk of progression or death than those with undetectable MRD (uMRD; Hazard Ratio[HR] = 3.67; 95% Credibility Interval [CrI] 3.34, 4.03; P < 0.01).

在个体水平上，可检测到MRD（dMRD）的受试者比无法检测到MRD（uMRD）的受试者进展或死亡的风险显著更高（风险比[HR] = 3.67；95%可信区间[CrI] 3.34, 4.03；P < 0.01）。

In contrast, MRD-testing results and PFS were weak at the trial-level (Spearman rho [R] = -0.33; Determination Coefficients [R² ] = 0.06), especially for BTKi- therapy (R = -0.05, R² = 0.03) and venetoclax-based therapies (R = -0.28, R² = 0.02).

相比之下，微小残留病灶（MRD）检测结果与无进展生存期（PFS）在试验级别上的相关性较弱（Spearman相关系数[R] = -0.33；决定系数[R²] = 0.06），尤其对于BTK抑制剂治疗（R = -0.05，R² = 0.03）和基于venetoclax的治疗（R = -0.28，R² = 0.02）。

Correlations were stronger for therapies involving drugs such as chemoimmunotherapy and/or monoclonal antibodies, where MRD tests of bone marrow (R = -0.94; R2 = 0.86) were more accurately predicted PFS than blood.

涉及化疗免疫治疗和/或单克隆抗体药物的治疗，相关性更强，其中骨髓微小残留病灶（MRD）检测（R = -0.94；R² = 0.86）比血液更能准确预测无进展生存期（PFS）。

In sensitivity analyses stratified by treatment approach we found a correlation of treatment-effect in fixed-duration therapy approaching the pre-specified validity threshold (R = -0.80 [-0.93, -0.53]; R² = 0.43, P < 0.01).

在按治疗方式分层的敏感性分析中，我们发现固定期限治疗的效果与预设的有效性阈值接近（R = -0.80 [-0.93, -0.53]；R² = 0.43，P < 0.01）。

Our data indicate the accuracy of MRD-testing results to surrogate PFS is context-dependent, influenced by treatment approach, therapy type, and the sampling source, and should be interpreted cautiously when informing clinical or regulatory decisions.

我们的数据表明，MRD检测结果作为无进展生存期（PFS）的替代指标的准确性是依赖于上下文的，受治疗方式、治疗类型和采样来源的影响，在指导临床或监管决策时应谨慎解释。